Ruthenium (II) complex cis-[Ru ^II (ŋ ² -O 2 CC 7 H 7 O 2 )(dppm) 2 ]PF 6 -hmxbato induces ROS-mediated apoptosis in lung tumor cells producing selective cytotoxicity.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Coordination Complexes/*pharmacology ; Lung Neoplasms/*drug therapy ; Ruthenium Compounds/*pharmacology; A549 Cells ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Coordination Complexes/chemistry ; DNA Damage ; Humans ; Leishmania/metabolism ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Membrane Potential, Mitochondrial/drug effects ; Reactive Oxygen Species/metabolism ; Ruthenium Compounds/chemistry

Ruthenium complexes have been extensively explored as potential molecules for cancer treatment. Considering our previous findings on the remarkable cytotoxic activity exhibited by the ruthenium (II) complex 3-hydroxy-4-methoxybenzoate (hmxbato)-cis-[Ru ^II (ŋ ² -O 2 CC 7 H 7 O 2 )(dppm) 2 ]PF 6 against Leishmania promastigotes and also the similar metabolic characteristics between trypanosomatids and tumor cells, the present study aimed to analyze the anticancer potential of hmxbato against lung tumor cells, as well as the partial death mechanisms involved. Hmxbato demonstrated selective cytotoxicity against A549 lung tumor cells. In addition, this complex at a concentration of 3.8 µM was able to expressively increase the generation of reactive oxygen species (ROS) in tumor cells, causing an oxidative stress that may culminate in: (1) reduction in cellular proliferation; (2) changes in cell morphology and organization patterns of the actin cytoskeleton; (3) cell arrest in the G2/M phase of the cell cycle; (4) apoptosis; (5) changes in the mitochondrial membrane potential and (6) initial DNA damage. Furthermore, we demonstrated that the induction of programmed cell death can occur by the intrinsic apoptotic pathway through the activation of caspases. It is also worth highlighting that hmxbato exhibited predominant actions on A549 tumor cells in comparison to BEAS-2B normal bronchial epithelium cells, which makes this complex an interesting candidate for the design of new drugs against lung cancer.

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0 (Antineoplastic Agents)
0 (Coordination Complexes)
0 (Reactive Oxygen Species)
0 (Ruthenium Compounds)

Date Created: 20200922 Date Completed: 20201217 Latest Revision: 20231112

20231112

PMC7506019

10.1038/s41598-020-72420-w

32958783